ClinVar Miner

Submissions for variant NM_000179.2(MSH6):c.3426G>A (p.Thr1142=) (rs747771350)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000491276 SCV000580182 likely benign Hereditary cancer-predisposing syndrome 2014-11-28 criteria provided, single submitter clinical testing
Color RCV000491276 SCV000685400 likely benign Hereditary cancer-predisposing syndrome 2015-04-13 criteria provided, single submitter clinical testing
Counsyl RCV000410566 SCV000488906 likely benign Hereditary nonpolyposis colorectal cancer type 5 2016-07-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590286 SCV000695863 uncertain significance not provided 2016-12-16 criteria provided, single submitter clinical testing Variant summary: The MSH6 c.3426G>A (p.Thr1142Thr) variant causes a synonymous change involving a non-conserved nucleotide that 5/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts the creation of an ESE binding site, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/121208, which does not exceed the estimated maximal expected allele frequency for a pathogenic MSH6 variant of 1/7037. The variant of interest has not, to our knowledge, been reported in affected individuals via publications, however, a clinical diagnostic laboratory classifies the variant as "likely benign." Therefore, the variant of interest has been classified as a "Variant of Uncertain Significance - Possibly Benign," until additional information becomes available (ie, clinical and functional studies).
Invitae RCV000227949 SCV000283802 likely benign Hereditary nonpolyposis colon cancer 2018-01-09 criteria provided, single submitter clinical testing
University of Washington Department of Laboratory Medicine,University of Washington RCV000758626 SCV000887383 likely benign Lynch syndrome 2018-05-01 criteria provided, single submitter clinical testing MSH6 NM_000179.2:c.3426G>A has a 0.9% probability of pathogenicity based on combining prior probability from public data with a likelihood ratio of 0.16 to 1, generated from evidence of seeing this as a somatic mutation in a tumor with loss of heterozygosity at the MSH6 locus. See Shirts et al 2018, PMID 29887214.

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